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Regulation of differentiation, proliferation and drug-induced apoptosis in HT58 lymphoma cells

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Pathology & Oncology Research

Abstract

Recently, it has been suggested, that differentiated cells are more resistant to the apoptotic effect of DNA damaging agents possibly due to the decreased activity of “damage detecting/apoptosis triggering” mechanism. Previously, we have shown, that PMA pretreatment reduced etoposide-(ETO) but enhanced staurosporine- (STA) -induced apoptosis in HT58 cells. Data presented here show that the HT58 human, “mature” B-lymphoma cells exposed to PMA secrete more IgM into the supernatant indicating commitment of cells to perform differentiated function. The sensitivity of HT58 cells to ETO- or STA-induced apoptosis is influenced diversely with PMA pre- or posttreatment. Interestingly, the DNA damage (gamma radiation, bleomycin, ETO) or okadaic acic (30 nM) reduced the [PMA+STA] - induced apoptosis.

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Abbreviations

BLEO:

bleomycin

CDK:

cyclin dependent kinase

CONT:

control

ETO:

etoposide

i-anti-IgM:

immobilized antihuman IgM antibody

OKA:

okadaic acid

PFC:

plaque forming cells

PI:

propidium iodide

PMA:

phorbol 12-myristate 13-acetate

RAD:

gamma irradiation

s-anti IgM:

solubilised anti-human IgM antibody

STA:

staurosporine

References

  1. Kaufmann SH: Induction of endonucleolitic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. Cancer Res 49:5870–5878, 1989.

    PubMed  CAS  Google Scholar 

  2. Hickman JA: Apoptosis induced by anticancer drugs. Cancer Metastat Rev 11:121–140, 1992.

    Article  CAS  Google Scholar 

  3. Zhivotovsky B, Burgess DH, Vanags DM and Orrenius M: Involvement of cellular proteolytic machinery in apoptosis. Biochem Biophys Res Comm 230:481–488, 1997.

    Article  PubMed  CAS  Google Scholar 

  4. Darzynkiewicz Z: Apoptosis in antitumor strategies: modulation of cell cycle or differentiation. J Cell Biochem 58:151–159, 1995.

    Article  PubMed  CAS  Google Scholar 

  5. Warrel RP, Frankel SR, Miller WH et al: Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-transretionic acid). New Eng J Med 324:1385–1393, 1991.

    Google Scholar 

  6. Studzinsky GP, Rathod B, Wang QM, et al: Uncoupling of cell cyle arrest from the expression of monocytic differentiation markers in HL60 cell variants. Exp Cell Res 232: 376–387, 1997.

    Article  Google Scholar 

  7. Bathia U, Traganos F and Darzynkiewicz Z: Induction of cell differentiation potentiates apoptosis triggered by prior exposure to DNA-damaging drugs. Cell Growth Differ 6:937–944, 1995.

    Google Scholar 

  8. Linette GP and Korsmeyer SJ: Differentiation and cell death: lesson from the immune system. Curr Opin Cell Biol 6:809–815, 1994.

    Article  PubMed  CAS  Google Scholar 

  9. Liu LF: DNA topoisomerase poisons as antitumor drugs. Annu Rev Biochem 58:351–375, 1989.

    Article  PubMed  CAS  Google Scholar 

  10. Fry AM, Chresta CM, Davies SM et al: Relationship between topoisomerase II level and chemosensitivity in human tumor cell lines. Cancer Res 51:6592–6595, 1991.

    PubMed  CAS  Google Scholar 

  11. Del Bino G., Skierski JS and Darzynkiewicz Z: The concentration-dependent diversity of the effect of DNA topoisomerase I and II on the cell cycle of HL-60 cells. Exp Cell Res 195:485–491, 1991.

    Article  PubMed  CAS  Google Scholar 

  12. Enoch T and Norbury C: Cellular responses to DNA damage: cell-cycle checkpoint, apoptosis and the roles of p53 and ATM. TIBS 20:426–430, 1995.

    PubMed  CAS  Google Scholar 

  13. Kharbanda S, Pandey P, ** S et al: Functional interaction between DNA-PK and c-Abl in response to DNA damage. Nature 386:732–735, 1997.

    Article  PubMed  CAS  Google Scholar 

  14. Dubrez L, Savoy I, Hamman A and Solary E: Pivotal role of a DEVD-sensitive step in etoposide-induced and Fas-mediated apoptotic pathways. EMBO J 15:5504–5512, 1996.

    PubMed  CAS  Google Scholar 

  15. Tamaoki T, Nomoto H, Takahashi I et al: Staurosporine, potent inhibitor of phospholipide/Ca++ dependent protein kinase. Biochem. Biophys. Res. Comm 135:397-402.

  16. Gadbois DM, Hamaguchi JR, Swank RA and Bradbury EM: Staurosporine is a potent inhibitor of p34CDC2 and p34CDC2-like kinases. Biochem Biophys Res Comm 184:80–85, 1992.

    Article  PubMed  CAS  Google Scholar 

  17. Yoshida M, Usui T, Tsujimura K et al: Biochemical difference between staurosporine-induced apoptosis and premature mitosis. Exp Cell Res 232:225–239, 1997.

    Article  PubMed  CAS  Google Scholar 

  18. Mihalik R, Farkas Gy, Kopper L, et al: Possible involvement of protein kinase C-epsylon in phorbol ester-induced growth inhibition of human lymphoblastic cells. Int J Biochem Cell Biol 28: 925–933, 1996.

    Article  PubMed  CAS  Google Scholar 

  19. Shi L, Nishioka WK, Th’ng J et al: Premature p34cdc2 activation required for apoptosis. Science 263: 1143–1145, 1994.

    Article  PubMed  CAS  Google Scholar 

  20. Mihalik R, Kopper L and Benczur M: Modulation of drug-induced apoptosis in a human B-lymphoma cell line (HT58). Immunol Lett 48:17–21, 1995.

    Article  PubMed  CAS  Google Scholar 

  21. Gamard CJ, Blobe GC, Hannun YA and Obeid LM: Specific role for protein kinase C beta in cell differentiation. Cell Growth Differ 5:405–409, 1994.

    PubMed  CAS  Google Scholar 

  22. Golding B, Pillemer SR, Roussou P et al: Inverse relationship between proliferation and differentiation in a human TNP-specific B cell line. J Immunol 131:2564–2568, 1988.

    Google Scholar 

  23. Kopper L, Bankfalvi A, Mihalik R. et al: New in vitro line from a human (B) non-Hodgkin lymphoma. Anticancer Res. 11:1645–1650, 1991.

    PubMed  CAS  Google Scholar 

  24. Kiss K, Uher F and Gergely J: A natural IgM antiboby does inhibit polyclonal and antigen specific IgM but not IgG B cell responses. Immunol. Lett 39:235–241, 1994.

    Article  PubMed  CAS  Google Scholar 

  25. Gronowicz E, Coutinho A, Melchers F: A plaque assay for cells secreting Ig of a given type or class. Eur J Immunol 6:588–593, 1976.

    Article  PubMed  CAS  Google Scholar 

  26. Mihalik R, Uher H, Berczi L et al: Detection of drug-induced apoptosis by flow cytometry after alcaline extraction of ethanol fixed cells. Pathol Oncol Res 2:78–83, 1996.

    Article  PubMed  CAS  Google Scholar 

  27. Coleman TR and Dunphy WG: cdc2 regulatory factors. Curr Opin Cell Biol 6:877–882, 1994

    Article  PubMed  CAS  Google Scholar 

  28. Wolf CM, Reynolds JE, Morana SJ and Eastman A: The temporal relationship between protein phosphatase, ICE/CED-3 proteases, intracellular acidification and DNA fragmentation in apoptosis. Exp Cell Res 230:22–27, 1997.

    Article  PubMed  CAS  Google Scholar 

  29. Lock RB: Inhibition of p34cdc2 kinase activation, p34cdc2 tyrosine dephosphorylation, and mitotic progression in Chinese hamster ovary cells exposed to etoposide. Cancer Res. 52:1817–1822, 1992.

    PubMed  CAS  Google Scholar 

  30. Lock RB, Thomson BS, Sullivan DM and Stribinskiene L: Potentiation of etoposide-induced apoptosis by staurosporine in human tumor cells is associated with events downstream of DNA-protein complex formation. Cancer Chemother Pharmacol 39:399–409, 1997.

    Article  PubMed  CAS  Google Scholar 

  31. Shimizu T, O’connor PM, Kohn KW and Pommier Y: Unscheduled activation of cyclin B1/cdc2 kinase in human promyelocytic leukemia cell line HL60 cells undergoing apoptosis induced by DNA damage. Cancer Res 55:228–231, 1995.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. 1st Institute Pathology and Experimental Cancer Research, Semmelweis University of Medicine, Üllői út 26, 1085, Budapest, Hungary

    Rudolf Mihalik, István PetÁk, Anna SebestyÉn & László Kopper

  2. National Institute of Hematology and Immunology, Budapest, Hungary

    Ferenc Uher

Authors
  1. Rudolf Mihalik
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  2. Ferenc Uher
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  3. István PetÁk
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  4. Anna SebestyÉn
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  5. László Kopper
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Correspondence to László Kopper.

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Mihalik, R., Uher, F., PetÁk, I. et al. Regulation of differentiation, proliferation and drug-induced apoptosis in HT58 lymphoma cells. Pathol. Oncol. Res. 3, 100–105 (1997). https://doi.org/10.1007/BF02907802

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  • DOI: https://doi.org/10.1007/BF02907802

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